Toll样受体与炎症性肠病

Toll like receptors and inflammatory bowel disease

Toll样受体(TLRs)是天然免疫系统中的细胞跨膜受体,可识别病原相关分子模式(PAMP)。不同的PAMP激活不同的TLR,TLR在髓样分化蛋白(MD2)、CD14辅助下,通过MyD88依赖型信号通路或非MyD88依赖型信号通路激活核因子-κB(NF-κB)、干扰素调节因子3/7(IRF3/7)及活化蛋白-1(AP-1),最终诱导下游目的基因表达。TLR对肠黏膜天然免疫反应调节发挥关键作用;而病原微生物在IBD的发生中起重要作用。生理情况下,肠上皮细胞持续表达TLR3和TLR5,而TLR2和TLR4几乎无法检测到;但在IBD患者的肠上皮细胞表面,却可检测到TLR2和TLR4的表达。随着对TLR信号通路研究和认识的不断深入,以TLR为靶点的药物研究也正成为一个热点。

Toll like receptors （TLRs） are transmembrane receptors playing important roles in innate immunity system and act as pattern recognition receptors for pathogen-associated molecular patterns （PAMPs）. Different PAMP activate different TLR. With the assistance of MD2, CD14, through MyD88 dependent signal pathway or the non-MyD88 dependent signal pathway, TLRs activate nuclear factor-κB （ NF-κB ）, interferon regulatory factor 3/7 （ IRF3/7 ） and activator protein-1 （ AP-1 ）, which ultimatelylead to the downstream gene expression. TLRs play a pivotal role in the innate immunity of intestinal mucosa. Under physiological conditions, the intestinal epithelial cells continuously express TLR3 and TLR5, while TLR2 and TLR4 are only barely detectable. Whereas TLR2 and TLR4 are expressed in intestinal epithelial cell surface with IBD, therefore, the dysregulation of TLR-mediated PAMP recognition could be related with the formation and development of IBD. To understand the complex mechanisms underlying Toll-like receptor signal pathway will provide additional data that might be helpful to devise novel therapeutic approaches for IBD.